The research program developed in this laboratory has as an overall objective the examination of changes in neuronal membrane receptors as a result of chronic alcohol exposure and of the role played by these receptor changes in the manifestations of ethanol dependence and withdrawal. Primary emphasis has been placed on the elucidation of ethanol effects on membrane receptors for the putative amino acid transmitters L-glutamic acid and GABA, and for the well established neurotransmitter acetylcholine. The in vitro studies have demonstrated an increase in the sensitivity of the putative glutamate receptors of brain synaptosomes from alcohol-treated rats, and a concomitant decrease in the sensitivity of the GABA binding sites. These changes can be viewed as the neuronal adaptation to the depressant effects of ethanol. These observations of ethanol-induced alterations in receptor binding capacity have been substantiated by in vivo demonstrations of the effectiveness of glutamate antagonists and GABA agonists in blocking withdrawal seizures after chronic alcohol exposure. Both the in vitro and the in vivo studies are being continued in order to explore in greater detail the mechanisms involved in the production of these receptor changes.